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Inhibitors “suicide” of the relaxed

The exchange of DNA between bacteria and helps them to evolve and adapt quickly to changing environment, but also constitutes a serious health problem since the same mechanism for transferring genes for resistance to antibiotics. In the case of transfer of resistance by bacterial conjugation, the protein that initiates the transfer of DNA (relaxase) is key to the process. Conjugative processing of DNA, makes a cut relaxase-specific site (nic site) in plasmid DNA transfer, being covalently bound to the 5 ‘end of nic site. Based on this cut, a mechanism of rolling circle replication produces DNA chain that is transferred to the cell container, while a second transesterification reaction, also catalyzed by relaxase, recircularize plasmid .

So, knowing in detail the biochemical reaction and three-dimensional structure of the relaxase, we can find inhibitors that prevent the transfer of DNA. However, this study of the biochemistry of the reaction has been limited by the rapid equilibrium between the cutting and religation reactions that prevents detailed study of the covalent intermediate formed.

In an article published in The EMBO Journal, the group formed by researchers at the University of Cantabria and the Institute of Biomedicine and Biotechnology of Cantabria have used oligonucleotides containing a 3′-S-link fosforotiolato the cleavage site recognized by the relaxase . This change allows the court after not produce a free 3′-OH group capable of attacking the tyrosine-phosphate bond produced the rapid religation oligonucleotide cut, but a free 3′-SH, that being a weak nucleophile can not produce this reaction relegation. These oligonucleotides ‘suicide’ move for both the reaction towards covalent adducts consider allowing the intermediate steps of the reactions catalyzed by the relaxase.